Accessing data to support pesticide residue and emerging contaminant analysis from US-EPA online dashboards

The US-EPA Center for Computational Toxicology and Exposure has been developing software and databases that serve the chemistry community for many years. This presentation will focus on several web-based software applications which have been developed at the USEPA and made available to the community. The primary software application from the Center is the CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard). The publicly accessible proof-of-concept Cheminformatics Modules (https://www.epa.gov/chemicalresearch/cheminformatics) provides access to multiple applications in development allowing for hazard comparison for sets of chemicals, structure-substructure-similarity searching, structure alerts and batch QSAR prediction of both physicochemical and toxicity endpoints. A number of other applications, presently in development but not publicly accessible will also be discussed. These include AMOS, the database of Analytical Methods and Open Spectra.
Analytical methods vary in nature from detailed regulatory methods to more summary in nature. Regulatory method documents can include details of analytes which can be studied, supported matrices, reagents, methodological details, statistical performance, interlaboratory validation and other details. Regulatory bodies including the US Environmental Protection Agency (US-EPA), US Geological Survey (USGS), US Department of Agriculture (USDA) and others provide detailed analytical methods and collections of summary methods from the agrochemical industry, such as the US-EPA Environmental Chemistry Methods (https://www.epa.gov/pesticide-analytical-methods/environmental-chemistry-methods-ecm). Instrument vendors also provide access to many hundreds of application notes which can be considered as summary methods. AMOS presently contains >5,000 methods integrated to their chemical structures and > 260,000 public domain mass spectral data. AMOS allows for filtering of methods based on analyte, chemical class, method source and other related metadata. AMOS is an important facet of the developing Non-Targeted Analysis WebApp presently also in development at the EPA.
This presentation will provide an overview of existing publicly accessible Dashboards and work in progress to support analysis of pesticides, veterinary drug residues, and other chemicals in food, animal feed, and environmental samples. This abstract does not necessarily represent the views or policies of the U.S. Environmental Protection Agency.

1. The views expressed in this presentation are those of the author and do not necessarily reflect the views or policies of the U.S. EPA Accessing Data to Support Pesticide Residue and Emerging Contaminant Analysis from US-EPA Online Dashboards Antony Williams ACS National Meeting, Denver, CO: August 2024

2. US EPA: Office of Research and Development Office of Research and Development (ORD) is the research arm of EPA Public health and environmental assessment Computational toxicology, exposure & modeling I work for the Center for Computational Toxicology and Exposure in the Computational Chemistry and Cheminformatics Branch

3. Free-Access Cheminformatics Tools The Center for Computational Toxicology and Exposure has delivered many tools including CompTox Chemicals Dashboard (primary tool from the center) Proof-of-Concept cheminformatics modules Chemicals Hazard Profiling Chemical Transformations Database Analytical Methods and Spectra Chemical Safety Profiling 2

4. Curating Chemistry into the DSSTox Database 3 Chemistry underpins all of our tools Data assembly and curation is critical DSSTox assembled over 25 years

5. CompTox Chemicals Dashboard https://comptox.epa.gov/dashboard/

6. The Charge for the Dashboard Develop a “first-stop-shop” for environmental chemical data to support EPA and partner decision making: Centralized location for relevant chemical data Chemistry, exposure, hazard and dosimetry Combination of existing data and predictive models Publicly accessible, periodically updated, curated Easy access to data improves efficiency and ultimately a ccelerates chemical risk assessment

7. Detailed Chemical Pages

8. Experimental and Predicted Data Physchem and Fate & Transport experimental and predicted data Data can be downloaded as Excel, TSV and CSV files

9. Chemical Hazard Data

10. Safety Data

11. Sources of Exposure to Chemicals

12. Chemical Lists (not all lists are created equal…)

13. Chemical Lists Chemical lists are focused on regulations, specific research efforts and categories 501 lists and growing TSCA Inventory Clean Water Act Hazardous Substances Consumer Products database Chemicals of Emerging Concern PFAS lists Extractables and Leachables …lists are versioned and updated and new lists added 12

14. What about Pesticides? 16 out of 501 lists 13

15. EPA OPPIN list of >4000 chemicals 14

16. Harvesting Data en masse How easy is it to harvest data for 4000 pesticides Physicochemical properties Fate and transport Toxicity values Bioactivity data in 100s of in vitro data Exposure data Chemical identifiers Links to regulatory assessments

17. Batch Searching

18. Batch Searching is a big enabler https://pubs.acs.org/doi/10.1021/acs.jcim.0c01273 17

19. Batch Search

20. Batch Search – Excel, CSV, SDF file

21. Batch Search

22. Filter chemicals and send to batch search 21

23. There is so much more… In vitro bioactivity data exposing our ToxCast/Tox21 data Exposure data with functional use information and chemical weight fractions in products Real-time QSAR predictions – draw your chemicals to predict 16 toxicity and physicochemical property endpoints Integration to realtime literature searches using Google Scholar and Pubmed Linking to >40 public domain databases 22

24. So now you know the Dashboard… 23

25. Lots of “proof-of-concept” tools in development PoCs are research software builds to prove approaches before moving into production software environments PoCs are to figure out how to address specific questions Assemble data, develop data model(s), test user interface approaches , work with test user base to garner feedback Since PoCs are internal access data refreshes and application updates can be more Underlying APIs are being used in our research 24

26. PoCs have been rebuilt for production Examples of PoCs integrated into production apps WebTEST predictions on the Dashboard Structure/substructure/similarity search 25

27. How to compare Hazard Data? 26

28. How to compare Hazard Data? NOT Easy to interpret… 27

29. Hazard Profile 28 Hazard Comparison module profiles toxicity across chemicals https://www.epa.gov/chemical-research/cheminformatics

30. Hazard Profile On-click view of underlying data 29

31. Data to Excel in <60s 30

32. Simple Analog “read-across” Suppose a chemical has limited data – perform an analog search to find related chemicals with data 31

33. Simple Analog “read-across” Similarity 32

34. Hazard Comparison Profiling 33

35. Hazard Comparison Profiling

36. Where can our tools be applied Emergency Response utility is obvious… Consider East Palestine 35 https://www.cleveland19.com/2023/02/14/ntsb-announces-preliminary-malfunction-that-caused-east-palestine-train-derailment/ POLYPROPYLENE POLYETHYLENE Residue lube oil VINYL CHLORIDE DIPROPYLENE GLYCOL PROPYLENE GLYCOL DIETHYLENE GLYCOL COMBUSTIBLE LIQ., NOS (ETHYLENE GLYCOL MONOBUTYL ETHER) SEMOLINA COMBUSTIBLE LIQ., NOS (ETHYLHEXYL ACRYLATE) POLYVINYL PETROLEUM LUBEOIL POLYPROPYL GLYCOL ISOBUTYLENE BUTYL ACRYLATES, STABILIZED PETRO OIL, NEC ADDITIVES, FUEL BALLS,CTN,M EDCL SHEET STEEL VEGTABLE, FROZEN BENZENE PARAFFIN WAX FLAKES, POWDER HYDRAULIC CEMENT AUTOS PASSENGER MALT LIQUORS

37. Cheminformatics Safety Module (NOT PUBLIC) Integrate multiple data streams… 36

38. EPA Measurement Data 37 Measurement data are needed to ensure chemical safety Characterize risk Regulate use & disposal Manage human & ecological exposures Ensure compliance under federal statutes Chemical Monitoring Needs Exposure Assessment Dose- Response Assessment Risk Characterization Hazard Identification

39. Applications of Exposomics at EPA Ongoing efforts applying NTA to exposomics challenges including PFAS identification Pesticides in various matrices CECs in water Biosolids Examples include… 38

40. Example 1: Consumer Product Analysis 39

41. Example 2: Recycled Product Analysis 40

42. Example 3: Placental Tissue Analysis 41

43. Applications of Exposomics at EPA Ongoing efforts applying NTA to exposomics challenges including PFAS identification Pesticides in various matrices CECs in water Biosolids Cheminformatics is a key component of NTA analysis Structure standardization (MS-Ready structure forms) Predictive models (LCMS amenability, retention time prediction) in silico mass spectrometry prediction Chemical Space Mapping Chemical Transformation database Analytical Methods and Open Spectral database 42

44. AMOS: Analytical Methods and Open Spectra (NOT PUBLIC yet) Simple Vision: I want to find the best method(s) associated with a chemical and/or class of chemicals Answer the question “I cannot find a method for my chemical” - HELP The Approach: Aggregate MS method documents (and adjust the definition of “what is a useful method”) Extract chemistry (mostly CASRN and Names) Map CASRN and Names to structures Deliver a proof-of-concept application to search a database by names, CASRNs, InChIKeys and ultimately structure 43

45. AMOS: Analytical Methods and Open Spectra (NOT PUBLIC yet) Three types of data in the database: Methods (regulatory, lab manuals and SOPs, publications, tech notes) Spectra (from public domain and our own laboratories) Monographs (harvested from SWGDRUG and other sites) Some methods have associated spectra Some data are just externally linked Currently contains around 673k spectra, 600k external links, >27k “Fact Sheets” and >5600 methods Spectra – LC-MS, GC-MS, NMR ALL data are growing in number with weekly releases 44

46. AMOS database

47. General Search – Mass Spectra 46

48. General Search – Mass Spectrum Metadata 47

49. 345 Pesticide Methods for 2705 substances 48

50. Functional Use Classifications – Directed Graph Visualization 49

51. …to find methods for those chemicals 50

52. Chemical Transformation Simulator Database 51

53. ChET : Chemical Transformations Database

54. ChET Reaction Map Lists 53

55. ChET Visual Reaction Maps Compare and overlap maps Load all maps containing a particular chemical Prune and filter maps 54

56. Conclusions Underpinning chemistry data is from the DSSTox database CompTox Chemicals Dashboard is public access to DSSTox and other related databases Proof-of-Concept (PoC) tools are built to prove approaches Everything is increasingly API driven and APIs are now public 55

57. Contact Information Contact info: [email protected] Slides available at: https://www.slideshare.net/AntonyWilliams/ Obtain articles from Google Scholar Profile 56